SODIUM VALPORIC ACID

Indications & Dose:

Seizures:

Children >10 years and Adults;

Oral Initial: 10-15 mg/kg/day in 1-3 divided doses; increase by 5-10 mg/kg/day at weekly intervals until therapeutic levels are achieved; maintenance: 3060 mg/kg/day.

Adult usual dose: 1000-2500 mg/day. Children receiving more than one anticonvulsant (ie, polytherapy) may require doses up to 100 mg/kg/ day in 3-4 divided doses

I.V.:  Administer as a 60-minute infusion (<20 mg/ minute) with the same frequency as oral products; switch patient to oral products as soon as possible. Alternatively, rapid infusions have been given: <15 mg/kg over 5-10 minutes (1.5-3 mg/kg/minute). Rectal (unlabeled): Dilute syrup 1:1 with water for use as a retention enema; loading dose: 17-20 mg/ kg one time; maintenance: 10-15 mg/kg/dose every 8 hours

Status epilepticus (unlabeled use):

Adults:

Loading dose: I.V.: 15-25 mg/kg administered at 3 mg/kg/minute.

Maintenance dose: I.V. infusion: 1-4 mg/kg/hour; titrate dose as needed based upon patient response and evaluation of drug-drug interactions

Mania:

Adults: Oral: 750-1500 mg/day in divided doses; dose should be adjusted as rapidly as possible to desired clinical effect; a loading dose of 20 mg/kg may be used; maximum recommended dosage: 60 mg/kg/day

Migraine prophylaxis:

Adults: Oral:

Extended release tablets: 500 mg once daily for 7 days, then increase to 1000 mg once daily; adjust dose based on patient response; usual dosage range 500-1000 mg/day Delayed release tablets: 250 mg twice daily; adjust dose based on patient response, up to 1000 mg/ day

Elderly: Elimination is decreased in the elderly. Studies of elderly patients with dementia show a high incidence of somnolence. In some patients, this was associated with weight loss. Starting doses should be lower and increases should be slow, with careful monitoring of nutritional intake and dehydration. Safety and efficacy for use in patients >65 years have not been studied for migraine prophylaxis. 

RENAL IMPAIRMENT: A 27% reduction in clearance of unbound valproate is seen in patients with Clcr, <10 mL/minute. Hemodialysis reduces valproate concentrations by 20%, therefore no dose adjustment is needed in patients with renal failure. Protein binding is reduced, monitoring only total valproate concentrations may be misleading.

HEPATIC IMPAIRMENT: Reduce dose. Clearance is decreased with liver impairment. Hepatic disease is also associated with decreased albumin

concentrations and 2- to 2.6-fold increase in the unbound fraction. Free concentrations of valproate may be elevated while total concentrations appear normal.

PREGNANCY RISK: Factor D

Contraindications:

Hypersensitivity to valproic acid, derivatives, or any component of the formulation; hepatic dysfunction; urea cycle disorders; pregnancy 

Side Effects:

Cautions:

Precautions:

Interaction:

Drugs Cytochrome P450 Effect: For valproic acid: Substrate (minor) of CYP2A6, 2B6, 2C8/9, 2C19, 2E1; Inhibits CYP2C8/9 (weak), 2C19 (weak), 2D6 (weak), 3A4 (weak); Induces CYP2A6 (weak) Increased Effect/Toxicity: Absence seizures have been reported in patients receiving VPA and clonazepam. Valproic acid may increase, decrease,or have no effect on carbamazepine and phenytoin levels. Valproic acid may increase serum concentrations of carbamazepine epoxide (active metabolite). Valproic acid may increase serum concentrations of diazepam, lamotrigine; nimOdipine, and phenobarbitsl, and tricyclic antidepressants. Chlorpromazine (and possibly other phenothiazines), macrolide antibiotics (clarithromycin, erythromycin, troleandomycin), felbamate, and isoniazid may inhibit the metabolism of valproic acid. Aspirin or other salicylates may displace valproic acid from protein-binding sites, leading to acute toxicity. 

Warnings:

Adverse Effects:

Lactations:

Enters breast milk/use caution 

Special Precautions:

Counselling:

Side Effects Or Adverse Reactions:

 Adverse reactions reported when used as monotherapy for complex partial seizure: >10%:

Central nervous system: Somnolence (18% to 30%), dizziness (13% to 18%), insomnia (9% to 15%), nervousness (7% to 11%)

Dermatologic: Alopecia (13% to 24%)

Gastrointestinal: Nausea (26% to 34%), diarrhea (19% to 23%), vomiting (15% to 23%), abdominal pain (9% to 12%), dyspepsia (10% to 11%), anorexia (4% to 11%)

Hematologic: Thrombocytopenia (1% to 24%)

Neuromuscular & skeletal: Tremor (19% to 57%), weakness (10% to 21%)

Respiratory: Respiratory tract infection (13% to 20%), pharyngitis (2% to 8%), dyspnea (1% to 5%) 1% to 10%

Cardiovascular: Hypertension, palpitation, peripheral edema (3% to 8%), tachycardia, chest pain

Central nervous system: Amnesia (4% to 7%), abnormal dreams, anxiety, confusion, depression (4% to 5%), malaise, personality disorder Dermatologic: Bruising (4% to 5%), dry skin, petechia, pruritus, rash

Endocrine & metabolic: Amenorrhea, dysmenorrhea

Gastrointestinal: Eructation, flatulence, hematemesis, increased appetite, pancreatitis, periodontal abscess, taste perversion, weight gain (4% to 9%)

Genitourinary:Urinary frequency, urinary incontinence, vaginitis

Hepatic: Increased AST and ALT

Neuromuscular & skeletal: Abnormal gait, arthralgia, back pain, hyperbola, incoordination, leg cramps, myalgia, myasthenia, paresthesia, twitching

Ocular: Amblyopia/blurred vision (4% to 8%), abnormal vision, nystagmus (1% to 7%)

Otic: Deafness, otitis media, tinnitus (1% to 7%)

Respiratory: Epistaxis, increased cough, pneumonia, sinusitis

Patient And Carer Advice: